Human brain activity invokes a complex interplay of neuron activity and spatiotemporal variations in metabolism, blood flow and blood oxygen level. These processes are functionally connected in neurovascular units of the brain, which are composed of integrated networks of neurons, astrocytes, and vascular smooth muscle cells. Impaired neurovascular coupling is implicated in stroke, hypertension, epilepsy, Alzheimer and Parkinson diseases and is the subject of intense biomedical research on network-level dynamics of human brain function. Current strategies for noninvasive neurovascular imaging focus on combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) and to a lesser degree on combined near-infrared spectroscopy (NIRS) and EEG or magnetoencephalography (MEG). There are however some fundamental limitations to existing multimodal neuroimaging approaches. The temporal resolution of fMRI, on the order of 0.5 Hz, limits the temporal precision of investigations into the dynamics of neurovascular coupling. NIRS overcomes the rate limitation of fMRI but is only sensitive to the outer regions of the cerebral cortex. Subject exclusion is a concern with MRI, which is unsafe for individuals with certain metal implants and is poorly tolerated by individuals with claustrophobia. Engineering advances are urgently needed to deliver spatially resolved, high-speed, matched imaging of neural and hemodynamic physiology. The objective of this project is to develop a new neuroimaging technology that meets these needs. The proposed system uses an innovative approach to integrating two capabilities of the superconducting quantum interference device (SQUID): biomagnetometer measurement of magnetic susceptibility and magnetoencephalography (MEG). Measuring neural activity with MEG is based on detecting the magnetic fields produced by active neurons. SQUID susceptibility measurement detects changes in the level of deoxygenated hemoglobin in the blood, similarly to fMRI, but with faster temporal sampling. An added benefit is that the proposed system is capable of high-precision dynamic imaging of magnetic nanoparticles, which opens up novel applications for targeted cancer therapies. Since the proposed system uses ultra-low field magnetics it may also be used to study neurovascular function in epilepsy for patients with implanted electrode arrays and in Parkinson disease for patients with implanted deep brain stimulation devices. This project specifically aims to optimize the spatial resolution and sampling rate of the proposed MEG-susceptometry system and to perform a comparative analysis between MEG-susceptometry and EEG-fMRI. The technological innovations from this project have the potential of delivering unprecedented precision and resolution in multimodal neuroimaging that will enable fundamental breakthroughs in neurovascular brain dynamics in normal and pathophysiological conditions. 1